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The Road to HPLC2018 Part IV: The Grand Challenge of Whole Proteins

The intact protein separations crucial for top-down mass spectrometry continue to thwart chromatographers – will we see progress in 2018?

John E. Wiktorowicz,
Neil Kelleher
|
02/09/2018

The essential questions of how and to what purpose we investigate proteomics are becoming ever more pressing as we unravel the complexity of the human genome and its relationship to the proteome. Recent analyses suggest that the human genome contains roughly 20,700 genes (1). However, the complexity of the human proteome also reflects multiple splice variants (2), which yield an estimated 205,000 protein-coding transcripts (3). With over 400 different types of post-translational modifications currently known, and without even contemplating the vast combinatorial universe that implies, there are at least 1,000,000 distinct protein forms within a given human cell (4).

The huge diversity of proteoforms and their post-translational modifications leads us to question what their functional role is. Could their dysfunction underlie many human diseases? Essentially, the entire spectrum of human cellular biology can be traced to protein-level post-translational modifications, but compared with the genome, the proteome is dramatically under-mapped.

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